Caffeine (1,3,7-trimethylxanthine) holds the dubious distinction of being the most widely used psychotropic drug in North America. The methylated purine is most often consumed in colas, teas, chocolates and numerous prescription and non-prescription drugs. Despite the ubiquitous consumption of the drug, we still do not know whether or not the drug is an important contributing "lifestyle" factor in the genesis of malignant disease. Such is the case with human breast tumors (benign and malignant); controversy still exists as to whether or not caffeine consumption contributes to human breast tumorigenesis. During the past 3 years, our studies provide evidence that caffeine consumption (via the drinking water) can indeed effect (inhibit and enhance) mammary gland tumorigenesis in experimental animals, a phenomenon that is dependent upon the time-span of caffeine treatment, the dose of caffeine used and the animal model examined. In this research proposal, we intend to further examine the role of caffeine in experimental animal (rat and mouse) mammary gland tumorigenesis. Specifically, we intend to: 1) further evaluate the role of caffeine in DMBA-induced rat mammary gland tumorigenesis and, in addition, examine the role of caffeine in the MNU-induced rat mammary carcinoma model and in the pregnancy- and hormone-induced mouse mammary carcinoma model. In addition, we intend to: 2) examine the influence of caffeine on normal mammary gland developmental growth processes in immature and mature mice and 3) determine the influence of caffeine on mammotropic hormone secretion in immature and mature rats. These studies are designed to extend our current understanding of the influence of caffeine on normal and neoplastic mammary gland developmental growth processes and provide insight into the mechanism by which the drug influences these processes.